Potentiation of the response to chemotherapy in patients with breast cancer by dietary supplementation with L-arginine: results of a randomised controlled trial.
Patients with large primary breast cancers are being treated with neo-adjuvant chemotherapy. Studies in animals have shown that responses to chemotherapy can be increased by dietary manipulation of tumour cell metabolism. Also dietary supplementation with the amino acid L-arginine, resulted in an increase in tumour metabolic activity expression of the nuclear activation antigen, Ki67, in patients with breast cancer. Therefore, we have carried out a randomised, double blind, placebo controlled trial to determine if L-arginine supplementation is beneficial in patients with breast cancer, undergoing neo-adjuvant chemotherapy. 96 patients were randomised to receive L-arginine (30 g/day) for three days (n = 48) or placebo (n = 48) prior to undergoing chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisolone), 6 pulses at 21-day intervals. Clinical and pathological responses were assessed in both groups of patients following completion of chemotherapy. The clinical response rate was 77% (23% complete and 54% partial responses) in the L-arginine treated group, compared with 71% (15% complete and 56% partial) in the placebo group of patients (p = ns). However, in patients with tumours less than 6 cm in initial diameter, there was a significant increase in the better histopathological responses in the L-arginine group, when compared with the placebo group of patients (88% vs 52%, p = 0.04). This may have important implications for clinical practice.
Heys
S D
SD
Surgical Nutrition and Metabolism Unit, Department of Surgery, University of Aberdeen, Aberdeen, UK.
Ogston
K
K
Miller
I
I
Hutcheon
A W
AW
Walker
L G
LG
Sarker
T K
TK
Dewar
J
J
Ah-See
A K
AK
Eremin
O
O
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004317:Doxorubicin / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D014750:Vincristine / Q000627:therapeutic use*
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D001120:Arginine; D011241:Prednisone